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Absence of hepatitis C virus transmission but frequent transmission of HIV-1 from sexual contact with doubly-infected individuals.

Hepatitis C virus (HCV) is transmitted through infected blood and blood products, but evidence of other routes of transmission is less clearly understood. In a study designed to examine human immunodeficiency virus (HIV) transmission, the prevalence of HCV has also been measured. Sixty-one couples were analysed, 30 in which partners were at risk through sexual contact alone, of whom 12 (40%) became infected with HIV and none with HCV. Thirty-one partners were exposed sexually and additionally through intravenous drug use. Of these, 16 (52%) became infected with HIV and 25 (80%) contracted HCV infection. These findings support the evidence of others that HCV is only rarely transmitted by sexual intercourse in heterosexual relationships and that HIV is not a co-factor for HCV transmission.

Adolescent↗

Transmission rates of hepatitis C virus by different batches of a contaminated anti-D immunoglobulin preparation.

BACKGROUND AND OBJECTIVES: The aim of this study was to determine the hepatitis C virus (HCV) infection rate of recipients of different batches of anti-D immunoglobulin associated with an outbreak of HCV infection which occurred in 1977 and its relationship to the polymerase chain reaction (PCR) status of the implicated batches. This study was undertaken to determine the predictive value of HCV genome detection and quantification for subsequent infection in recipients of an HCV-contaminated anti-D immunoglobulin product for intravenous use. MATERIALS AND METHODS: Sera from recipients of anti-D were tested by HCV enzyme immunoassay and if found positive were subsequently tested by recombinant immunoblot assay and HCV PCR in a national HCV anti-D screening programme set up in 1994. The HCV status of 1,342 known recipients of infectious or potentially infectious batches has been compared to the amount of HCV RNA in the anti-D batch they received so as to determine the value of PCR in the prediction of infectivity in immunoglobulin preparations. RESULTS: It has been demonstrated that HCV-infected plasma derived from batches of anti-D showing levels of viral genome in excess of 10(4) genomes per millilitre led to infection of up to 60% of recipients. In contrast, batches with undetectable levels of HCV genome very rarely transmitted infection. CONCLUSIONS: The presence of HCV RNA in intravenous immunoglobulin preparations which have not undergone a specific viral inactivation step is a predictor of HCV infection in recipients.

Disease Outbreaks↗

Auto-immune Addison's disease in identical twins.

Identical male twins are described, one of whom presented with clinical symptoms of Addison's disease whereas the other was shown to have a deficient adrenal cortical response to stimulation tests. Both had positive adrenal cortex antibodies.

Addison Disease↗

Prevalence of hepatitis C genotypes among patients with chronic hepatitis C in Norway. Construct Group.

Among 116 patients with biopsy-confirmed chronic hepatitis C (Riba 2 or Riba 3 positive) in a multicenter study in southern Norway on interferon, we determined hepatitis C virus genotype by restriction fragment length polymorphism (RFLP) of the 5' NCR. The RFLP method was supplemented by and compared with a serological typing method based on the detection of type-specific antibody to peptide from the NS-4 region. A total of 102/106 (96%) patient sera showed detectable type-specific antibody to NS-4 peptides and corresponded in all cases, except two, to the genotype detected by polymerase chain reaction. Combining the results from RFLP genotyping and serotyping, genotype 1 was found in 40 (35%) (27 with 1a and 10 with 1b, 3 subtypes not determined), genotype 2 in 15 (13%) (subtype 2b in 14 and 1 subtype not determined), and genotype 3 in 58 (50%) of patients. The low mean age of the patients (34 years), the low prevalence of cirrhosis (3.5%), the short duration of the disease, and a high prevalence of intravenous-drug abusers may account for the low prevalence of infection with genotype 1b (9%). The epidemiological features of hepatitis C patients are markedly different from patient groups described in southern Europe in terms of risk factors, age, and genotype distribution.

Adult↗

Detection of a novel DNA virus (TTV) in blood donors and blood products.

BACKGROUND: A newly discovered DNA virus, transfusion-transmitted virus (TTV), has been implicated as a cause of post-transfusion hepatitis. We investigated the frequency of TTV viraemia in UK blood donors, and the extent to which TTV contaminates blood products such as factor VIII and IX clotting factors. We also investigated the possible aetiological role of TTV in cryptogenic fulminant hepatic failure (FHF). METHODS: We extracted DNA from plasma of blood donors and patients with FHF, and from blood products (factor VIII and IX clotting-factor concentrates, immunoglobulin preparations). We detected TTV by PCR using primers from a conserved region in the TTV genome. FINDINGS: TTV viraemia was detected in 19 (1.9%) of 1000 non-remunerated regular blood donors. Infection occurred more frequently in older donors (mean age 53 years), compared with the age prolife of donors infected with hepatitis C virus and other parenterally-transmitted viruses. TTV contamination was found in ten (56%) of 18 batches of factor VIII and IX concentrate manufactured from such non-remunerated donors, and in seven (44%) of 16 batches of commercially available products. Whereas solvent or detergent treatment had little effect on the detection of TTV in factor VIII and IX by PCR, this virucidal step seemed to inactivate TTV infectivity. TTV infection was detected in four (19%) of 21 patients with FHF; in three cases, infection was detected at the onset of disease and could thus not be excluded from its aetiology. INTERPRETATION: TTV viraemia is frequent in the blood-donor population, and transmission of TTV through transfusion of blood components may have occurred extensively. Clinical assessment of infected donors and recipients of blood and blood products, and assessment of TTV's aetiological role in hepatic and extra-hepatic disease, are urgently needed.

Adult↗

A complicated case of metastatic teratoma. Growing teratoma syndrome and cerebral metastasis.

All patients presenting with metastatic teratoma should be regarded as potentially curable and this case demonstrates the multiple treatment modalities which are often needed in the management of such patients. Increasing experience with cisplatin based combination chemotherapy has led to the development of prognostic factors which are used to determine the intensity of treatment given to individual patients. Surgical intervention plays a very important role in the management of residual disease at the completion of chemotherapy. Recognition of the growing teratoma syndrome and the importance of early surgical excision is illustrated by this case. Isolated CNS relapse may occur because the CNS may act as a sanctuary site in patients receiving systemic chemotherapy, but does not preclude long term disease free survival.

Antineoplastic Combined Chemotherapy Protocols↗

Hereditary hyperuricemia and renal disease.

Hyperuricemia and gout have long been known to run in families. As well as an apparently multifactorial genetic component to classic gout itself, 2 rather unusual sex-linked single-gene disorders of purine biosynthesis or recycling have been defined: deficiency of the enzyme hypoxanthine-guaninephosphoribosyl transferase (HPRT), and overactivity of PPriboseP synthase. Both result in overproduction of urate, hyperuricemia, and secondary overexcretion that may lead to acute or chronic renal damage. Familial juvenile hyperuricemic nephropathy (FJHN) and autosomal-dominant medullary cystic kidney disease (ADMCKD) are more common but less well-defined hyperuricemic conditions resulting from a decrease in the fractional excretion of filtered urate, with normal urate production. Although having features in common, ADMCKD is distinguished in particular by the presence of medullary cysts. One major group of both disorders is associated with mutations in the gene for uromodulin, but this accounts for only about one third of cases, and genetic heterogeneity is present. Whether the genes involved in these latter disorders contribute to the polygenic hyperuricemia and urate underexcretion of classic gout remains unexplored.

Genetic Predisposition to Disease↗

Early growth and death from cardiovascular disease in women.

OBJECTIVE: To determine whether the link suggested between growth in utero and during infancy and death from cardiovascular disease in men is also present in women. DESIGN: Follow up study of women and men whose birth weight and weight at 1 year of age had been recorded. SETTING: Hertfordshire, England. SUBJECTS: 5585 women and 10,141 men born during 1911-30. MAIN OUTCOME MEASURES: Standardised mortality ratios for cardiovascular disease. RESULTS: Among women and men death rates from cardiovascular disease fell progressively between the low and high birth weights groups (chi 2 = 4.3, p = 0.04 for women, chi 2 = 8.5, p < 0.005 for men). Cardiovascular deaths in men but not women were also strongly related to weight at 1 year, falling progressively between the low and high weight groups (chi 2 = 27.5, p < 0.0001). The highest cardiovascular death rates in women were among those with below average birth weight but above average weight at 1 year. In men the highest rates were among those with below average birth weight and below average weight at 1 year. CONCLUSION: Relations between cardiovascular disease and birth weight are similar in men and women. In men cardiovascular disease is also related to weight gain in infancy.

Aged↗

The role of the RAS in programming of adult hypertension.

The aetiology of cardiovascular disease originally included two components: a genetic component and an environmental or lifestyle component. Increasing epidemiologic evidence has been accumulating during the last decades indicating the importance of a third component: the influence of the environment during foetal development. Poor living conditions resulted in a high infant mortality and influenced the incidence of cardiovascular diseases in adulthood despite better living conditions (A. Forsdahl. Br J Prev Soc Med 1977; 31, 91-95). An association between pre-natal growth pattern and the rate of death from cardiovascular disease in adulthood was reported (D.J. Barker, P.D. Winter, C. Osmond, B. Margetts & S.J. Simmonds. Lancet 1989; 2, 577-580). Men from Hartfordshire (UK), born between 1911 and 1930 were investigated. The investigations showed that men with the lowest weight at birth and at 1 year of age had the highest risks of death from cardiovascular disease (D.J. Barker, P.D. Winter, C. Osmond, B. Margetts & S.J. Simmonds. Lancet 1989; 2, 577-580). These findings suggested that factors in the perinatal environment could programme an individual for later risk of development of cardiovascular disease compared with someone born with a normal weight. Numerous studies have since confirmed these initial findings of an inverse relationship between early growth pattern and cardiovascular disease in adulthood.

Animals↗

First day serum creatine kinase BB isoenzyme in high-risk infants.

Serum creatine kinase BB (CK-BB) on the 1st day of life was measured by radioimmunoassay in 37 very low birth weight (VLBW) infants, 14 severely asphyxiated infants and 24 controls. The 31 survivors from the two high-risk groups were followed up for 12 months or more. VLBW non-survivors (n = 14) had significantly higher mean CK-BB levels than survivors (n = 23), (P less than 0.05). However, if only survivors were considered, CK-BB was a poor discriminator of outcome in either study group. First day serum CK-BB is not a useful predictor of neurodevelopmental outcome in surviving high-risk infants.

Asphyxia Neonatorum↗